Toxoplasma gondii

Author: MBLOGSTU

Introduction

Toxoplasma gondii is a zoonotic protozoan infection with a reservoir in mammals and birds. Transmission to humans occurs via ingestion of tissue cysts in poorly cooked meat of infested animals or via ingestion of oocysts shed in the feces of the definitive host (felines), which then contaminate the environment.

As an obligate intracellular protozoan, T. gondii can infect all mammals (which serve as intermediate hosts). In immunocompetent individuals, 90% of infections are asymptomatic. When symptoms occur, they often resemble a mononucleosis-like illness—characterized by low-grade fever, malaise, headache, and cervical lymphadenopathy.

More severe manifestations (such as encephalitis, myocarditis, hepatitis, and pneumonia) are rare but may complicate acute toxoplasmosis. In pregnant women, infection with T. gondii can be transmitted to the fetus, potentially causing permanent damage such as retinochoroiditis and hydrocephalus. Congenital infection when the mother is infected just prior to conception is extremely rare; even during the first few weeks of pregnancy, maternal–fetal transmission rates are only a few percent.

Epidemiology

The prevalence of toxoplasmosis varies greatly around the world. Prevalence rates depend on factors such as food production and harvesting practices, water treatment, environmental conditions, climate, and exposure to soil or sand.

Although Toxoplasma gondii occurs worldwide, its incidence is higher in tropical areas and decreases with increasing latitude.

There is no biological test to distinguish infections acquired from oocysts (transmitted by felines) versus those acquired by ingesting tissue cysts from infected meat. Thus, epidemiological surveys examining risk factors in infected versus non-infected individuals remain a valuable tool for assessing the importance of various sources of human infection.

For example, a prospective case–control study from Norway (1992–1994) found that eating raw or undercooked meat, poor kitchen hygiene, cleaning cat litter boxes, and consuming unwashed raw vegetables or fruits were all associated with an increased risk of T. gondii infection.

Morphology

Tachyzoites

The term “tachyzoite” (from the Greek "tachos" meaning speed) was coined by Frenkel to describe the rapidly multiplying stage of T. gondii that appears in virtually any cell of the intermediate host and in non-intestinal epithelial cells of the definitive host. This term has replaced “trophozoite” and is sometimes also referred to as endodyozoites or endozoites. Aggregates of numerous tachyzoites are called clones, terminal colonies, or groups.

Tachyzoites are often crescent shaped, approximately 2 by 6 μm, with a pointed anterior (conoidal) end and a rounded posterior end.

Ultrastructurally, tachyzoites contain a range of organelles and inclusion bodies—including a pellicle (outer covering), apical rings, polar rings, a conoid, rhoptries, micronemes, a micropore, mitochondria, subpellicular microtubules, endoplasmic reticulum (both rough and smooth), a Golgi complex, ribosomes, a nucleus (usually central with chromatin clumps and a central nucleolus), dense granules, and sometimes amylopectin granules. They also contain a multiple-membrane–bound plastid-like organelle (alternatively known as a Golgi adjunct or apicoplast).

Bradyzoites

The term “bradyzoite” (from the Greek "brady" meaning slow) was also coined by Frenkel to describe the stage that multiplies slowly within tissue cysts; these are sometimes referred to as cystozoites.

Within tissue cysts, bradyzoites reproduce by endodyogeny. Tissue cysts vary in size:

• Young tissue cysts may be as small as 5 mm in diameter and contain only two bradyzoites.
• Older cysts can contain hundreds of organisms.

In the brain, tissue cysts are often spheroidal and rarely exceed 70 μm in diameter, whereas intramuscular cysts are elongated and may be up to 100 μm long. Although cysts can develop in visceral organs (e.g., lungs, liver, and kidneys), they are most commonly found in neural and muscular tissues—including the brain, eyes, and skeletal and cardiac muscles. Intact tissue cysts typically do not provoke an inflammatory response and may persist for the lifetime of the host.

Oocyst

Unsporulated oocysts are subspherical to spherical with dimensions of approximately 10 by 12 μm. Under light microscopy, the oocyst wall is composed of two colorless layers; polar granules are absent, and the sporont nearly fills the oocyst.

Sporulation occurs outside the cat within 1 to 5 days after excretion, depending on aeration and temperature. Sporulated oocysts are subspherical to ellipsoidal, measuring about 11 by 13 μm in diameter. Each sporulated oocyst contains two ellipsoidal sporocysts (which lack Stieda bodies). Sporocysts are approximately 6 by 8 μm, each containing four sporozoites. A sporocyst residuum is present, while an oocyst residuum is absent.

Pathogenesis

Toxoplasma gondii has the ability to invade nearly any nucleated cell, establishing a productive infection. The initial step in this invasion is recognition and attachment to the target cell. Upon encountering a host cell, the parasite surveys the cell membrane until an appropriate point of attachment is recognized at its apical pole.

Host cell laminin, parasite laminin, parasite surface lectins, and major surface proteins (such as P30, also known as SAG-1, a glycosylphosphatidylinositol-anchored antigen) help mediate this preliminary attachment. Two types of organelles at the parasite's anterior—rhoptries and micronemes—then play key roles during invasion.

Further details on invasion: The exact mechanisms triggering microneme content discharge remain unclear. ROP1, a rhoptry protein secreted during invasion, associates with the membrane of the developing parasitophorous vacuole. Additionally, microneme proteins MIC-1 and MIC-2, which contain thrombospondin-like domains, likely assist in adhesion once released on the parasite’s surface. Recently, phospholipase-A2 has also been implicated in host cell invasion. After attachment, an annular junction forms between the parasite and host cell membrane, permitting the parasite to forcibly penetrate while drawing the membrane around it. The parasite then becomes enclosed within a parasitophorous vacuole derived from the host cell.

Extracellular tachyzoites are highly susceptible to oxygen intermediates, pH changes, and osmotic fluctuations; they are also killed by specific antibodies in the presence of complement. Most surface antigens and membrane-anchored proteins of T. gondii are integrated into the plasma membrane via glycosylphosphatidylinositol (GPI) anchors.

Clinical Manifestations

Congenitally acquired toxoplasmosis presents with a wide variety of signs and symptoms. In most cases, an infant is either asymptomatic or displays subclinical symptoms at birth, making the condition difficult to detect. A smaller subset of infants presents with overt neonatal symptoms, while others develop signs within the first few weeks or months of life. A history of hydrocephalus, retinochoroiditis, and central nervous system calcifications in the newborn period should alert the clinician to the possibility of toxoplasmosis. Reported symptoms include convulsions, palsies, growth or mental retardation, visual or hearing impairment, learning disabilities, organomegaly, lymphadenopathy, fever, and rash.

Ocular Toxoplasmosis

Toxoplasmosis commonly affects the retina and the underlying choroid, leading to retinochoroiditis—the most frequent manifestation of ocular toxoplasmosis. This condition is characterized by macular-pigmented lesions with a central necrotic area visible on funduscopic examination. In over 50% of congenital cases, lesions are unilateral and located on the posterior pole of the retina. Clinical findings may include a gray-white area of retinal necrosis (with or without exudates), adjacent optic disc swelling, vitreitis, vasculitis, and hemorrhage. The term “headlight in the fog” is often used to describe the appearance of retinal inflammation viewed through an opacified vitreous.

Central Nervous System Toxoplasmosis

In congenitally exposed infants, central nervous system (CNS) toxoplasmosis may present with or without overt neurologic symptoms. Reported manifestations include convulsions, abnormal tearing, nystagmus, strabismus, hearing or visual impairments, as well as growth and developmental delays. Many of these symptoms overlap with those of ocular toxoplasmosis. Additionally, toxoplasmosis can lead to hydrocephalus and microcephaly in the developing fetus.

Diagnosis

The prevention and treatment of congenital toxoplasmosis begins with the identification of infection in pregnant women through antibody testing that measures IgG and IgM levels.

IgG and IgM levels typically rise within 2 weeks of exposure. Elevated IgG indicates exposure but cannot distinguish between recent and past infection, as IgG persists at a low level throughout life. IgM antibodies, while generally present after acute infection, may remain high for up to 18 months in some individuals, potentially confounding the timing of exposure.

Because congenital toxoplasmosis is primarily a risk when the mother acquires the infection during pregnancy, a significant rise in specific antibody titers—or seroconversion—is considered diagnostic of recent exposure.

Despite serologic evidence of recent infection, confirmation should be obtained from a reference laboratory due to concerns about the sensitivity and specificity of available IgG and IgM tests. The Sabin–Feldman Dye test, which detects changes in T. gondii–specific IgG titers over a 3‑week period or a single elevated titer above 250 IU/ml (or a four‑fold increase), is considered the gold-standard. Polymerase chain reaction (PCR) testing of amniotic fluid is the preferred method to confirm fetal exposure, while PCR of cerebrospinal fluid can confirm CNS infection after birth.

Prevention

Prevention of Toxoplasma gondii infection involves measures such as proper food handling, thoroughly cooking meat, washing fruits and vegetables, and practicing good kitchen hygiene. Additionally, care should be taken when cleaning cat litter boxes to avoid accidental ingestion of oocysts.

Treatment

Treatment strategies for toxoplasmosis depend on the patient’s immune status and whether the infection is congenital. In general, immunocompetent patients with mild disease may not require treatment, whereas congenitally acquired or severe cases are managed with specific antiparasitic regimens. (Specific treatment protocols and drugs, such as pyrimethamine and sulfadiazine, can be added here as needed.)